Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017160 (gastroenteritis)
 11,398 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aminopeptidase-N (APN) has been identified [B. Delmas, J. Gelfi, R. L'Haridon, L. K. Vogel, H. Sjostrom, O. Noren, and H. Laude, Nature (London) 357:417-420, 1992] as a major receptor for porcine transmissible gastroenteritis virus (TGEV). Binding of TGEV to villous enterocytes from the jejuna of newborn pigs is saturable and at a higher level than that of binding of virus to newborn cryptal enterocytes or to enterocytes from older piglets (H. M. Weingartl and J. B. Derbyshire, Vet. Microbiol. 35:23-32, 1993). The distribution of APN in enterocytes in the jejuna of neonatal and 3 week-old-piglets, as determined by the measurement of enzymatic activity and by labeling of the cells with an anti-APN monoclonal antibody, did not correspond with the reported distribution of saturable binding sites on enterocytes. Monoclonal antibodies, which were prepared against plasma membranes derived from enterocytes harvested from the upper villi of newborn pigs, blocked the replication of TGEV, but not the porcine respiratory coronavirus, in ST cells and immunoprecipitated a 200-kDa protein in ST cell lysates. This protein was demonstrated by immunohistochemistry and by fluorescence-activated cell scanning to be present on the villous enterocytes of newborn pigs but to be lacking on the cryptal enterocytes of newborn pigs and on the villous and cryptal enterocytes of 3-week-old piglets. Since this distribution of the protein corresponds to the previously demonstrated distribution of saturable binding sites, we conclude that the 200-kDa protein may be an additional receptor for TGEV which is restricted to the villous enterocytes of newborn pigs and which contributes to the age sensitivity of these animals to the virus.
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PMID:Evidence for a putative second receptor for porcine transmissible gastroenteritis virus on the villous enterocytes of newborn pigs. 793 8

Swine enteric diseases have caused significant economic loss and have been considered as the major threat to the global swine industry. Several coronaviruses, including transmissible gastroenteritis virus (TGEV) and porcine epidemic diarrhea virus (PEDV), have been identified as the causative agents of these diseases. Effective measures to control these diseases are lacking. The major host cells of transmissible gastroenteritis virus and porcine epidemic diarrhea virus have thought to be epithelial cells on small intestine villi. Aminopeptidase-N (APN) has been described as the putative receptor for entry of transmissible gastroenteritis virus and porcine epidemic diarrhea virus into cells in vitro. Recently, Whitworth et al. have reported that APN knockout pigs are resistant to TGEV but not PEDV after weaning. However, it remains unclear if APN-null neonatal pigs are protected from TGEV. Here we report the generation of APN-null pigs by using CRISPR/Cas9 technology followed by somatic cell nuclear transfer. APN-null pigs are produced with normal pregnancy rate and viability, indicating lack of APN is not embryonic lethal. After viral challenge, APN-null neonatal piglets are resistant to highly virulent transmissible gastroenteritis virus. Histopathological analyses indicate APN-null pigs exhibit normal small intestine villi, while wildtype pigs show typical lesions in small intestines. Immunochemistry analyses confirm that no transmissible gastroenteritis virus antigen is detected in target tissues in APN-null piglets. However, upon porcine epidemic diarrhea virus challenge, APN-null pigs are still susceptible with 100% mortality. Collectively, this report provides a viable tool for producing animals with enhanced resistance to TGEV and clarifies that APN is dispensable for the PEDV infection in pigs.
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PMID:Aminopeptidase N-null neonatal piglets are protected from transmissible gastroenteritis virus but not porcine epidemic diarrhea virus. 3151 98